Prior U.S. Pat. Nos., such as 3,567,390, 4,152,391, 4,445,391, 4,507,997 and 4,896,546, as well as 3,567,389, 3,991,055 and 4,702,889, provide examples of metering and transfer valve assemblies wherein internal measuring (metering) chambers are provided, generally in the form of passageways. In U.S. Pat. No. 3,567,390, a metering and transfer valve assembly is provided having a pair of outer disc members and a central disc member sandwiched therebetween, its opposite surfaces being frictionally engaged with the facing surfaces of the respective outer disc members. The discs are aligned axially and mounted on a spindle so that the outer discs are stationary while the center disc is rotatable between two positions. A pair of axially parallel measuring through passageway sets are provided in the central disc and matching passageways are provided so that in one position of the central disc, liquid sample is received within one measuring passageway of one set. The central disc is rotated to a second position where a precise volume of the liquid sample is isolated as an aliquot from the flow path of the said liquid sample and placed in communication with a second flow path. A precise predetermined volume of diluent is directed through the second flow path from a source exterior of the valve assembly. The sample aliquot is flushed from the valve assembly along with the predetermined volume of diluent and delivered to a mixing bath which carries electronic sensing means. After mixing, the mixture, now a precise dilution of the original liquid sample and comprising a diluted liquid suspension of the particles in said sample, is tested by passing same through the sensing means, same being a Coulter sensing aperture.
Simultaneous with the introduction of the liquid sample, a portion of the dilution is retrieved from the mixing bath and transferred to one measuring passageway of the second set of measuring passageways. When the central disc is rotated to isolate the aforementioned liquid sample aliquot, the "first" dilution is isolated in said one measuring passageway of said second set. When diluent is employed to flush a first dilution from the valve assembly, a predetermined precise known volume of diluent is employed to flush the measured portion of the prior made first dilution from the valve assembly to form a second dilution which is delivered to another testing location. The diluent volumes are premeasured exterior of the valve assembly and delivered to the valve assembly when needed. The testing is sequential per sample, the prior made "second dilution" being tested simultaneously with the testing of a current-made "first" dilution. Both sets of the segmenting passageways are formed in the central or rotatable disc of the valve assembly. Any reagents employed are introduced by means exterior of the valve assembly and delivered only into the mixing baths, never appearing within the valve assembly so as to avoid contamination of the flow paths within said assembly that are traversed by either the sample or the diluent.
A similar valve is provided in U.S. Pat. No. 3,567,389 with the use of spring means to maintain the valve elements in frictional sealed face to face engagement and wherein the spring means is relaxed slightly to permit rotation of one element relative the others for changing the relationship of the interior passageways defining one or another of the flow paths through the valve assembly. The tightened engagement of the facing surfaces was intended to avoid leakage during flow of the liquids along the flow paths..alignment likewise being maintained. Precise milling of the facing surfaces have been instituted with good effect to obtain a satisfactory sealed surface to surface engagement. Thus, Karas, U.S. Pat. No. 3,681,998, provided a hard, wear resistant surface for each of facing valve element surfaces with careful lapping of said surfaces to assure a leakproof seal therebetween. Even then, Karas also provided spring bias to maintain the said relationship. Nevertheless, such care in preparing the facing surfaces did not fully solve the problem since uneven wear resulted which limited the useful life of the valve assembly, necessitating service calls and likely early replacement of the valve assemblies. These valves also were not required to perform a multiplicity of functions, that is provision of measured samples were few and the necessary dilutions provided also were few. Not many flow paths were necessary and few passageways were required which had to be accommodated and aligned without interference ones with others.
Firman et al., U.S. Pat. No. 3,489,011 provided a slide liquid metering and transfer valve assembly formed of a pair of valve elements arranged one being slidable over the other, four pairs of ports being provided in the body and four cavities provided in the slide. Moving the slide from one position to a second position effected segmentation of a stream liquid from one pair of ports to transfer the segmented portion to a testing stream for analysis. In the embodiments therein disclosed, there were provided multiple chambers and multiple paths through which liquid flow was passed for segmentation, solvent being introduced to the segmented portions for transporting the combination to a destination. The valve assembly was limited to operation upon a flowing continuous stream of liquid or gaseous fluid, did not store the segmented portions as isolated portions, only delivered the segmented portions with accompanying solvent, i.e. used the solvent to propel the segmented portion from the valve assembly, did not provide for introduction to the valve of any corrosive or reactive reagent to pass therethrough, and provided no means to assure against misalignment or to prevent leakage from the passageway junctions of any liquid or gaseous fluid.
Isreeli et al, U.S. Pat. No. 3,583,232, did provide a "sampling" valve assembly formed of a pair of disc elements arranged coaxially in face to face engagement, one being a rotor and the other being a stator. The disc elements carried through passageways defining flow paths for passage of liquid sample, of a pilot fluid and air. A body of liquid sample was introduced and segmented into precise sample portions, loops were provided within which these portions were isolated and stored. However, only the sample liquid was metered and the pilot fluid was introduced to flush the isolated samples to a testing location. Air was introduced to separate the samples one from the others. No means was provided by Isreeli et al. to guard against or to prevent leakage from the internal passageway junctions, no other liquids were segmented to form metered volumes and stored within the valve assembly for delivery separate from the stored sample.
In U.S. Pat. No. 4,152,391, there is provided a metering and transfer valve assembly capable of forming three dilutions. This assembly comprises a pair of stationary disc members, stators, and a center, rotatable disc member, the rotor, sandwiched between the stators. The rotor carries one set of axially parallel, through segmenting passageways. A pair of external measuring loops are carried by the rotor, said loops passing through slots formed in one of the stators. The loops carry a precise volume of the liquid sample. One of the loops and the segmenting passageway of said one set are arranged to define a continuous flow path for the liquid sample during the loading of the valve assembly. The other loop is capable also of defining a continuous flow path with said segmenting passageway but the loops are parallel one relative to the other so that at least two aspirations, or loading steps, are required to provide the desired dilutions, alternatively.. The valve assembly also included internal gallery formations defining paths for communicating with selected passageways. Slots are necessarily formed in the stators in order to permit passage of the loops therethrough when the stators and rotor are arranged coaxially mounted on a shaft (or spindle) to enable rotation of the rotor relative to the stators for effecting the isolations of the precise sample volumes. Diluent for forming the dilutions is metered exterior of the valve assembly and introduced thereinto generally by means of pump operated dispensers.
U.S. Pat. No. 4,445,391 provided a liquid metering and transfer valve assembly wherein a measuring loop was secured to one of the stators in additional to the set of axially parallel segmenting passageways formed in the rotor. A series path was defined through the valve assembly including the loop and one of the set of segmenting passageways so that single loading step sufficed to fill both loop and segmenting passageway. With rotation of the rotor, a precise volume of liquid sample was isolated in said segmenting passageway and in said loop. An exteriorly metered volume of diluent was introduced respectively to the loop and to the said segmenting passageway to drive the isolated volumes of liquid sample, each with the known volume of diluent, to the testing location as respectively precise dilutions. The loop has only one function, that is, to meter the liquid sample volume. All other liquid volumes were measured exterior of the valve assembly and introduced as premeasured into the valve assembly. Reagents that were utilized as a part of the testing procedure were stored, measured and delivered from locations exterior of the valve, by-passing the valve assembly. Thus plural metering units, pumps, pinch and check valves, as well as considerable number of individual conduits, usually plastic tubing, were required resulting in complex arrangements and requiring considerable interior dedicated space, hence reducing the capable of achieving the compactness long sought.
U.S. Pat. No. 4,957,008 provided loop means for measuring and storing diluent, and for measuring small volumes of sample and storing same within axially parallel passageways within the valve assembly but the resulting assembly did not provide means for performing all of the fluid moving functions within the said assembly. No changes were provided for the facing surface to surface relationship to prevent leakage after a prolonged use. No provision was made for handling reagents such as lysing reagents within the valve, handling steps such as metering, storing and transporting such reagents within the valve assembly without contaminating other flow paths therewithin. Further, the number of functions required to be performed within the valve were less than those required to perform all functions expected of the system.
Surface to surface wear was not eliminated and though 30 the useful life expectancy was satisfactory, improvements were nevertheless desired but not attainable. Positive means for preventing eventual leakage was not provided. It should be pointed out that the many prior art metering and transfer valve assemblies heretofore provided for the metering and transfer of precise volume liquid sample portions, particularly those for use in hematological studies and analyses, have not provided means for introducing corrosive reagents, such as lysing agents, into the valve assembly, metering precise volume portions and isolating same within said valve assembly and delivering said isolated portions from said valve assembly, after passing therethrough, to an exterior chamber for mixing with the blood samples delivered from the valve assembly.
When considering control, storage and transfer valve assemblies for use as means to control, meter, store and deliver precise and accurate quantities of fluids with a minimum of carryover, the valve elements have been assembled in face to face sealed, frictional engagement with the expectation that the fluids, ordinarily liquids, pass from flow paths in one element to selectively matched flow paths in the other valve element so that these fluids will flow across the junctions of said flow paths without leakage thereat, and, further, that the result will maintain the integrity of the fluids, particularly where these fluids are different. Accomplishment of such goal requires that the different fluids be maintained segregated ones from the others with no unintentional intermixtures. It has been found that such results or goals most often fail to be achieved.
It has been discovered that among the causes of such failure has been the forces generated by the translation of one valve element relative to the others during the operation of the valve assembly to place one set of flow paths in communication with another selected set of flow paths in controlling the flow through said valve assembly. Where there are many such translatory operations, avoidance of intermixtures of the respective fluids becomes critical, yet such avoidance has not yet been accomplished.
Applicant has recognized that such aforementioned forces tend to vary, however minimally, the relative disposition of the said engaged surfaces sufficiently to break the surfaces seals established between said surfaces, such disruption effecting the maintaining of the segregation of the fluids and result in cross-contamination effects. In addition to the possible cross-contamination effects, the fluids tend to pass along said surfaces, leaking from the valve assembly to the exterior thereof and escape into the surrounding environment. This is a significant hazard, particularly where the fluids are those which are hazardous to the environment and/or the operator(s). Exposure to such fluids, contact of the operator(s) therewith and/or contamination of the environment may be dangerous, such as would occur if the fluids are biological fluids and may contain communicable disease causal elements.
U.S. Pat. Nos. 2,656,508 and 3,549,994 describe some of the analytical systems of the general type employing fluid metering and transfer valve assemblies offered by certain ones of those described in the prior art reviewed above. These systems are capable of many uses in the medical, biological, chemical and allied fields, in research as well as routine testing and require means which can produce liquid mixtures of specific concentration accurately, repeatedly and automatically. Such systems are required to perform measurements on a continuous basis with many tests made simultaneously and complex routines repeated with precision but with different samples. Systems of the type described have been utilized to obtain a plurality of parameters of whole blood, for example, and include means for operating a plurality of valves, pumps, hydraulic circuits, sensing and analytical means whereby a whole blood sample is subtended to provide predetermined aliquots thereof of which respectively are directed to locations where they are diluted, lysed, measured and discharged. The requisite liquid samples must be drawn and precisely measured, combined with preselected volumes of diluent to define requisite precise dilutions thereof, the dilutions being transferred to vessels within the system which contain sensing means for generating signals, which, in turn, are directed to analyzing apparatus for determining the desired characteristic parameters sought. Often different degrees of dilution are required for determination of the different parameters of the original sample. Sample quantities often are limited and hence the multiple operations and deterinations preferably are performed utilizing a single liquid sample of relatively small volume. Conservation of sample is a desired goal. The number of fluids required, the distances required for the fluids to travel within the system, the complexity of the fluid circuits within the system, the necessity of providing plural pumps, pinch valves and fluid conduits within the system, all require a relatively large assemblage necessitating housing means of substance occupying considerable space.
Certain of the determinations require mixture of the sample with selected reagents, some of which may be corrosive in nature so that the sample, as well as any portion of the system, is protected from contamination by or exposure to such reagent. In addition, considerable care must be undertaken in handling of the liquids, particularly the corrosive reagents and the liquid samples, to avoid any dispersal thereof in the exterior environment adjacent the assemblage and to avoid contact of said sample with the person of the operator. Splashing, scattering or other dispersal of the sample or other contamination of the environment about the installation desirably must be avoided.
Leakage of sample and/or other liquids within or about the system should be greatly minimized, preferably eliminated. In such systems, the operations involved in providing the sample aliquots, the dilution of each sample aliquot respectively, and the transfer and delivery of said respective diluted sample aliquots to the sensing means of the system have been performed by metering and transfer valve assemblies offered by certain of the aforementioned United States patents.
It is highly desirable to retain valve integrity throughout the operation thereof, to provide a construction where the quantity of sample required to provide the necessity aliquots thereof can be significantly reduced, where air leakage into the valve assembly as well as accumulation of debris is avoided, where sample carryover is materially minimized, where the size of the assemblage also is reduced with attendant reduction of the space required by the assemblage comprising the system and where the versatility of the system considerably is increased, say by the elimination of the multiplicity of pumps, control valves, conduit and the like which are encountered in commercial units. Accordingly, it would be highly desirable but not yet available, to provide a valve assembly which is multi-functional, precise and accurate and is capable of performing the liquid handling within its confines.
Multifunctional valves generally require plural interior passageways in one valve element which are matched with selected cooperating passageways in another valve element, to define flow paths crossing the junctions of said respective passageways. Each of the flow paths are carefully related to the other flow paths and may be traveled by related or different liquids, for example. The more functions being performed by and/or within the valve assembly, the more distinct flow paths requiring more passageways are necessary. Not only must there be coordination of the valve elements so that proper passageways are aligned at the proper stage in the operation of the said valve assembly, the relative alignments at the passageway junctions must be exact, precision and accuracy of mating being critical. Precise relationships must be maintained, notwithstanding relative movement of the valve elements. This precision must be maintained over the useful life of the valve assembly, notwithstanding wear on the interior surfaces during use thereof.
Of further advantage, it would be desirable, but not as yet available, to provide a valve assembly that will operate with the entire system being a closed system, liquid being unable to escape the system to that a non-polluted environment can be provided with the protection of the integrity of the results, the atmosphere and the operating personnel.
It should be noted that apparatus embodying systems of the character heretofore available may range from the relatively early, less complex and relatively small units to large, most complex units requiring considerable dedicated space, as a greater number of parameters for determination are required with improvements, such as in medical and scientific knowledge and technology, are developed and more complex determinations and information must be obtained. Such apparatus share a common requirement for increased .quantities of pumps, pinch valves, check valves, myriads of individual conduits for connections and cross-connections, manifolds, plural media storage containers, switching devices, etc., increasing the bulk of the apparatus, including its operational control, sensing, monitoring and data receiving and/or storage, analytical and delivery functional means.
Accordingly, the art has long sought apparatus of the character described which is a less complex nature yet which is capable of providing the many analytical functions which are provided by the use of the most highly complex and often bulky units available presently to the art. Reduction in size and complexity is a long sought after goal while retaining the precision, versatility, accuracy and reliability enjoyed with the more massive, highly complex units now available.
In addition, it would be desirable to provide a system of the character and purpose described which would possess increased versatility, would be capable of employment in a modular mode enabling operational coupling with a number of different modular operational units and results in an analyzing instrument which is compact, highly reliable, provides precise and accurate results, is easily serviced and maintained and is capable of being packaged as a materially reduced size unit as compared with prior instruments.